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J. Cell Sci. 121 (6): 804-813

Research Article

The PKC{delta} -Abl complex communicates ER stress to the mitochondria – an essential step in subsequent apoptosis

Xin Qi, and Daria Mochly-Rosen*

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA

* Author for correspondence (e-mail: mochly{at}stanford.edu)

Accepted for publication 19 December 2007.

Abstract: Conditions that compromise protein folding in the endoplasmic reticulum trigger the unfolded protein response (UPR), which either restores proper protein folding or results in cellular demise through apoptosis. In this study, we found that, in response to ER stress in vivo and in vitro, PKC{delta} translocates to the ER where it binds to the tyrosine kinase Abl. Tyrosine phosphorylation and kinase activity of PKC{delta} are required for PKC{delta} binding to Abl in the ER. Moreover, we found that inhibition of PKC{delta} by the PKC{delta}-specific peptide inhibitor {delta}V1-1 or by silencing of PKC{delta} reduces ER-stress-induced JNK activation and inhibits ER-stress-mediated apoptosis. Furthermore, the inhibitor of PKC{delta} kinase activity rottlerin blocks the translocation of the PKC{delta}-Abl complex from the ER to the mitochondria and confers protection against apoptosis. Thus, PKC{delta} communicates ER stress to the mitochondria by binding to ER-localized Abl. The PKC{delta}-Abl complex then translocates to the mitochondria, communicating ER stress to this organelle, thereby, triggering apoptosis.

Key Words: Protein kinase C • Apoptosis • Abl • Endoplasmic reticulum • Mitochondria

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Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)